The point is well made(even in passing) that iron deficient heart failure patients assigned to treatment with intravenous iron experience significantly lower rates of infection than counterparts not allocated to that treatment modality[1]. Even outside the context of congestive heart failure(CHF) iron deficiency has been shown to be associated with increased risk of infection[2]. The latter study explored the risk of infection according to levels of serum iron, transferrin saturation(TS), and serum ferritin. After multivariate adjustment, low TS at or below the fifth percentile(ie TS 11% or below) was associated with increased risk of any infection compared with TS between the 26th and the 74th percentile(ie TS 18.1-27.9)(Hazard Ratio 1.18; 95% Confidence Interval 1.10-1.26). More specifically, in that study , where >90% of infection-related deaths were attributable to pneumonia, low TS was also associated with increased risk of pneumonia(Hazard Ratio 1.20;95% CI 1.09-1.32)[2]..
In the cardiology context, infective endocarditis(IE), a disorder often complicated by CHF, can, itself, occur in association with iron deficiency(ID).
The following are examples of the association of IE and ID:-
(i)Association of IE and nutritional ID was documented in a 19 year old woman with a history of volitional anorexia and wight loss.
Iron deficiency was characterised by TS of 10%. She was initially given a diagnosis of anorexia nervosa and was pr...
The point is well made(even in passing) that iron deficient heart failure patients assigned to treatment with intravenous iron experience significantly lower rates of infection than counterparts not allocated to that treatment modality[1]. Even outside the context of congestive heart failure(CHF) iron deficiency has been shown to be associated with increased risk of infection[2]. The latter study explored the risk of infection according to levels of serum iron, transferrin saturation(TS), and serum ferritin. After multivariate adjustment, low TS at or below the fifth percentile(ie TS 11% or below) was associated with increased risk of any infection compared with TS between the 26th and the 74th percentile(ie TS 18.1-27.9)(Hazard Ratio 1.18; 95% Confidence Interval 1.10-1.26). More specifically, in that study , where >90% of infection-related deaths were attributable to pneumonia, low TS was also associated with increased risk of pneumonia(Hazard Ratio 1.20;95% CI 1.09-1.32)[2]..
In the cardiology context, infective endocarditis(IE), a disorder often complicated by CHF, can, itself, occur in association with iron deficiency(ID).
The following are examples of the association of IE and ID:-
(i)Association of IE and nutritional ID was documented in a 19 year old woman with a history of volitional anorexia and wight loss.
Iron deficiency was characterised by TS of 10%. She was initially given a diagnosis of anorexia nervosa and was prescribed oral iron and optimised nutritional intake. Three months later she presented with fever and refractory anaemia. Digital clubbing was noted, and she had a systolic murmur.. Blood cultures were positive for Streptococcus sanguinis, and echocardiography revealed vegetations on the mitral valve and tricuspid valve. Despite a variety of IE-related complications she responded well to mitral valve replacement, tricuspid valve repair and antibiotics and remained well on 1 year follow up[3].
(ii)Colon cancer was the underlying cause of both ID and IE in a 72 year old man who presented with fever, anaemia and an aortic systolic murmur. Blood cultures tested positive for Group G Streptococcus. Echocardiography showed an aortic valve vegetation.. The presence of ID "prompted further workup" that included colonoscopy. The latter disclosed the presence of colonic carcinoma..
(iii)Colon cancer was the underlying cause of both ID and IE despite the absence of a murmur in a 63 year old man who presented with fever and anaemia.. Blood cultures tested positive for Streptococcus bovis. On hospital day 3 he developed sudden onset hemiparesis. Subsequent echocardiography revealed mitral regurgitation and a mitral valve vegetation.. Colonoscopy revealed presence of carcinoma of the ascending colon[5].
Comment
(i)In the absence of heart failure, the association of ID and IE can occur in the context of an underlying cause of ID ranging from dietary deficiency to chronic gastrointestinal bleeding.
(ii)This scenario can be extrapolated to the CHF context
(iii)Accordingly, in addition to documenting the presence of ID in CHF patients, regardless of presence or absence of concomitant anaemia, clinicians should ascertain the underlying cause of ID, and should also be vigilant for IE as a complication of ID. This means regular auscultation for murmurs, bearing in mind the caveat that severe anaemia can be associated with so-called haemic murmurs even in the absence of valve disease, and that IE can be present even in the absence of a murmur. Confusingly as well, severe iron deficiency anaemia can be complicated by anaemic retinopathy characterised by the occurrence of Roth spots[6], the latter an ophthamological feature more commonly associated with IE.
References
[1]Squire I., Kalra PR
Cardiologists and recognition of iron deficiency in patients with heart failure
Heart 2025
Article in Press
[[2]Mottelson M., Glentho A., Nordestgaard BG et al
Iron, hemochromocytosis genotypes, and risk of infections: acohort study n of 142188 general population individuals
Blood 2024;144:693-
[3]Soh BW., Salim A., O'Riordan R., Owens P., Matiullah S
Unveiling the devastation of Streptococcus sanguinis infective endocarditis masquerading as iron deficiency anaemia: a case report
Eur Heart J Case Reports 2024;8:ytae388
[4]Abugroun A., Zughul R., Tawadrous M., Rodriguez M
Group G Streptococcus endocarditis in association with colon cancer
Cardiol Res 2018;8:59-62
[5] Riyaaz AAA., Samarasinghe R., Sellahewa KK., Sivakumaran S., Tampoe MS
Native valve streptococcus bovis endocarditis and refractory transfusion-dependent iron deficiency anameia associated with concomiant carcinoma of the colon: A case report and review of the literature
Case Reports in Infectious Diseases 2016;doi.org/10.1155/2016/2670307
[6]Fluss R., Zguri L., Rahme R., Fulger H
Iron-deficiency anemia causes an ischemic stroke in a young man
CUREUS 2019 11;11:e4218 DOI 10.7759/cureus 4218
Bridging the Gap: Improving Iron Deficiency Management in Heart Failure
The article by Su et al. offers an in-depth exploration of the persistent gaps in the knowledge and management of iron deficiency (ID) among cardiologists treating heart failure (HF) patients in China. This study not only highlights deficiencies in adherence to evidence-based guidelines but also underscores systemic and educational barriers that hinder optimal care.
The findings are striking: over half of the cardiologists surveyed were unaware of the need to routinely screen for ID in HF patients, and only a fraction understood the critical diagnostic role of transferrin saturation (TSAT). Alarmingly, less than 1% identified TSAT <20% as a standalone criterion for diagnosing ID, despite its established prognostic significance. This lack of awareness reflects a larger, global challenge in implementing ID management protocols, which are consistently linked to improved outcomes in HF patients.
Equally concerning is the predominant reliance on oral iron supplementation, with 68% of respondents favoring it over intravenous (IV) iron. This preference persists despite robust evidence from clinical trials demonstrating the superior efficacy of IV iron in improving functional capacity, quality of life, and reducing HF hospitalizations. Barriers to IV iron use—ranging from limited availability of recommended formulations like ferric carboxymaltose to misconceptions about adverse effects—f...
Bridging the Gap: Improving Iron Deficiency Management in Heart Failure
The article by Su et al. offers an in-depth exploration of the persistent gaps in the knowledge and management of iron deficiency (ID) among cardiologists treating heart failure (HF) patients in China. This study not only highlights deficiencies in adherence to evidence-based guidelines but also underscores systemic and educational barriers that hinder optimal care.
The findings are striking: over half of the cardiologists surveyed were unaware of the need to routinely screen for ID in HF patients, and only a fraction understood the critical diagnostic role of transferrin saturation (TSAT). Alarmingly, less than 1% identified TSAT <20% as a standalone criterion for diagnosing ID, despite its established prognostic significance. This lack of awareness reflects a larger, global challenge in implementing ID management protocols, which are consistently linked to improved outcomes in HF patients.
Equally concerning is the predominant reliance on oral iron supplementation, with 68% of respondents favoring it over intravenous (IV) iron. This preference persists despite robust evidence from clinical trials demonstrating the superior efficacy of IV iron in improving functional capacity, quality of life, and reducing HF hospitalizations. Barriers to IV iron use—ranging from limited availability of recommended formulations like ferric carboxymaltose to misconceptions about adverse effects—further complicate the adoption of best practices.
The article goes beyond identifying gaps; it also provides a roadmap for improvement. Educational initiatives aimed at increasing awareness of guideline-based ID definitions and treatments are urgently needed. Specialized training programs and HF clinics could play a pivotal role in integrating ID management into routine care. Additionally, systemic reforms to enhance access to advanced iron formulations and secure reimbursement for these therapies would address logistical and financial barriers.
To the editor: Zhang et al. provide a fascinating observational study showing that weight loss among obese UK Biobank participants with cardiovascular disease may not be beneficial [1]. The authors specifically highlight the following point “Maintaining a stable weight in obese people with cardiovascular disease may reduce the risk of mortality” [1]. Evidence from a large trial has shown that the weight loss drug semaglutide reduces mortality amongst the overweight/obese with pre-existing cardiovascular disease [2]. It is possible that some of the benefits of semaglutide could be driven by factors other than weight loss, given some benefits are evident before substantial weight has occurred [2]. However, some of the benefits of semaglutide are undoubtedly due to weight loss making Zhang et al.’s observations puzzling.
Zhang at al.’s study is an observational study of weight change in obese people with cardiovascular disease [1], so it is essentially a case series. Inference from case series is seen as the least reliable type of observational evidence [3]. Correspondingly, Zhang et al.’s study of the role of weight change in obese people with cardiovascular disease [1] is open to both the major sources of bias in causal inference, i.e., to confounding and selection bias [4].
Specifically, Zhang et al.’s study is open to confounding by obesity because obesity is likely a common cause of weight change and death. The study is also open to selection bias because...
To the editor: Zhang et al. provide a fascinating observational study showing that weight loss among obese UK Biobank participants with cardiovascular disease may not be beneficial [1]. The authors specifically highlight the following point “Maintaining a stable weight in obese people with cardiovascular disease may reduce the risk of mortality” [1]. Evidence from a large trial has shown that the weight loss drug semaglutide reduces mortality amongst the overweight/obese with pre-existing cardiovascular disease [2]. It is possible that some of the benefits of semaglutide could be driven by factors other than weight loss, given some benefits are evident before substantial weight has occurred [2]. However, some of the benefits of semaglutide are undoubtedly due to weight loss making Zhang et al.’s observations puzzling.
Zhang at al.’s study is an observational study of weight change in obese people with cardiovascular disease [1], so it is essentially a case series. Inference from case series is seen as the least reliable type of observational evidence [3]. Correspondingly, Zhang et al.’s study of the role of weight change in obese people with cardiovascular disease [1] is open to both the major sources of bias in causal inference, i.e., to confounding and selection bias [4].
Specifically, Zhang et al.’s study is open to confounding by obesity because obesity is likely a common cause of weight change and death. The study is also open to selection bias because the mean age at recruitment was 56.6 years [1], so the study only includes those who survived obesity and cardiovascular disease to recruitment. Typically, such selection on survival to recruitment biases towards the null or even gives estimates in the opposite direction to the true association. Given these possible biases and the lack of consistency with trial evidence [2], Zhang et al.’s study should not be interpreted as providing evidence that maintaining a stable weight in obese people with cardiovascular disease may reduce the risk of mortality.
1. Zhang J, Schutte R, Pierscionek B. Association of weight change with cardiovascular events and all-cause mortality in obese participants with cardiovascular disease: a prospective cohort study. . Heart. 2025;10.1136/heartjnl-2024-324383.
2. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232.
3. Greenhalgh T. How to read a paper. Getting your bearings (deciding what the paper is about). BMJ. 1997;315(7102):243-6.
4. Bareinboim E, Pearl J. Causal inference and the data-fusion problem. Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7345-52.
Economou Lundeberg et al report a U-shaped association between individuals estimated sodium intake and premature ventricular complexes (1). The estimate of individual sodium intake is based on a single fasting spot urine sodium value and the Kawasaki formula (1). The authors claim that the method is valid in part because the urine samples were collected in the fasting state and that the results have a correlation with 24-hr urine sodium excretion and blood pressure (1).
However, extensive consistent evidence, as repeatedly reviewed by major international scientific organizations, indicates single spot urine sodium values with estimating equations (including those using fasting urine samples and the Kawasaki equation) are not a valid method of assessing an individual’s dietary sodium (2-4). The method has very high random and systematic errors (2, 4, 5). The systematic errors have been shown to alter a linear association of dietary sodium and health outcomes (blood pressure and cardiovascular disease) including to a U or J shaped curve and to have associations with health outcomes when a constant sodium value is inserted in the equation rather than a real value (2-5). The changes in disease associations and disease associations independent of the sodium variable have been shown in several data bases and are mathematically predictable.
The random error is reflected by very low accuracy and reproducibility. For example, in a reanalysis of the validation of...
Economou Lundeberg et al report a U-shaped association between individuals estimated sodium intake and premature ventricular complexes (1). The estimate of individual sodium intake is based on a single fasting spot urine sodium value and the Kawasaki formula (1). The authors claim that the method is valid in part because the urine samples were collected in the fasting state and that the results have a correlation with 24-hr urine sodium excretion and blood pressure (1).
However, extensive consistent evidence, as repeatedly reviewed by major international scientific organizations, indicates single spot urine sodium values with estimating equations (including those using fasting urine samples and the Kawasaki equation) are not a valid method of assessing an individual’s dietary sodium (2-4). The method has very high random and systematic errors (2, 4, 5). The systematic errors have been shown to alter a linear association of dietary sodium and health outcomes (blood pressure and cardiovascular disease) including to a U or J shaped curve and to have associations with health outcomes when a constant sodium value is inserted in the equation rather than a real value (2-5). The changes in disease associations and disease associations independent of the sodium variable have been shown in several data bases and are mathematically predictable.
The random error is reflected by very low accuracy and reproducibility. For example, in a reanalysis of the validation of the PURE study from China (using the Kawasaki equation and a fasting sample), those initially categorized in the lowest quartile of sodium intake on initial spot urine assessment had a 58% error and a 104% error on the second assessment and 68% of those initially classified as in the lowest quartile were in a higher quartile on second assessment (6). The reference used to support their use of the Kawasaki equation as being ‘accurate with minimum bias’ concludes “Kawasaki’s formula is … not suitable for estimating individual sodium excretion”(1, 7). These concerns have been addressed in prior correspondence with some of the co-authors and in my opinion should at a minimum been discussed as limitations. (8, 9).
1. Economou Lundeberg J, Wuopio J, Mente A, Måneheim A, Okrajni M, Healey JS, et al. Estimated sodium intake and premature ventricular complexes: data from the population-based Swedish CArdioPulmonary bioImage Study. Heart. 2025:heartjnl-2024-324391.
2. Campbell NRC, He FJ, Tan M, Cappuccio FP, Neal B, Woodward M, et al. The International Consortium for Quality Research on Dietary Sodium/Salt (TRUE) position statement on the use of 24-hour, spot, and short duration (<24 hours) timed urine collections to assess dietary sodium intake. J Clin Hypertens (Greenwich). 2019;21:700-9.
3. Cappuccio FP, Campbell NRC, He FJ, Jacobson MF, MacGregor GA, Antman E, et al. Sodium and health: old myths, and a controversy based on denial. Curr Nutr Rep. 2022;11:172-84.
4. Campbell NRC, Whelton PP, Orias M, Cobb LL, Jones ESW, Garg R, et al. It is strongly recommended to not conduct, fund, or publish research studies that use spot urine samples with estimating equations to assess individuals’ sodium (salt) intake in association with health outcomes: a policy statement of the World Hypertension League, International Society of Hypertension and Resolve to Save Lives. J Hypertens. 2023;41:683-6.
5. Ji C, Sykes L, Paul C, Dary O, Legetic B, Campbell NRC, et al. Systematic review of studies comparing 24-hour and spot urine collections for estimating population salt intake. Rev Panam Salud Publica. 2012;32(4):307-15.
6. McLean RM, Song J, Wang C, He FJ, Cappuccio FC, Campbell NRC, et al. Formula-led methods using first morning fasting spot urine to assess usual salt intake: a secondary analysis of PURE study data. J Hypertens. 2024;42:2003-10.
7. Han W, Sun N, Chen Y, Wang H, Xi Y, Ma Z. Validation of the Spot Urine in Evaluating 24-Hour Sodium Excretion in Chinese Hypertension Patients. Am J Hypertens. 2015;28(11):1368-75.
8. Campbell NRC, He FJ, McLean RM, Cappuccio FP, Woodward M, GA M. Dietary sodium and cardiovascular disease in China: addressing the authors’ response, statements and claims. J Hypertens. 2022;40:1831-6.
9. Campbell NRC, He FJ, Cappuccio FP, MacGregor GA. Dietary sodium 'controversy'—issues and potential solutions. Cur Nutr Rep. 2021;10(3):188-99.
Given the disparity between the number of patients in apixaban(4261 patients) and the number of patients on edoxaban(76 patients)[1] it was not possible to make a meaningful comparison between the two agents especially because, in other contexts, edoxaban has been utilised in doses ranging from 15 mg/day to 6o mg/day in people with atrial fibrillation(AF){2],{3]. Accordingly, to lump edoxaban with other direct oral anticoagulants(DOACS) in the comparison with warfarin, as Mitchell et al have done(fig 4)[1[] does not do justice to the safety profile of edoxaban.
In the comparison undertaken by Eikelboom et al between the safety profile of warfarin and individual DOACs the 30 mg/day dose of edoxaban was cited as being associated with significantly lower risk of gastrointestinal bleeding than warfarin(Hazard Ratio 0.67; 95% Confidence Interval 0.53-0.83)[2]. This was the dose recommended in patients with body weight 60 kg or less[2].
In the ELDERCARE-AF randomised clinical care comprising 984 atrial fibrillation patients of mean age 86 a comparison was made between edoxaban 15 mg/day versus placebo. Edoxaban was associated with significantly lower rates of stroke and systemic embolism than placebo, both in frail elderly patients(p=0.02 ) and in non frail elderly(p=0.002), respectively.
References
[1]Mitchell A., Watson M., Welsh TJ., McGrogan A
Safety and effectiveness of anticoagulation therapy in older people with atrial fibrillation d...
Given the disparity between the number of patients in apixaban(4261 patients) and the number of patients on edoxaban(76 patients)[1] it was not possible to make a meaningful comparison between the two agents especially because, in other contexts, edoxaban has been utilised in doses ranging from 15 mg/day to 6o mg/day in people with atrial fibrillation(AF){2],{3]. Accordingly, to lump edoxaban with other direct oral anticoagulants(DOACS) in the comparison with warfarin, as Mitchell et al have done(fig 4)[1[] does not do justice to the safety profile of edoxaban.
In the comparison undertaken by Eikelboom et al between the safety profile of warfarin and individual DOACs the 30 mg/day dose of edoxaban was cited as being associated with significantly lower risk of gastrointestinal bleeding than warfarin(Hazard Ratio 0.67; 95% Confidence Interval 0.53-0.83)[2]. This was the dose recommended in patients with body weight 60 kg or less[2].
In the ELDERCARE-AF randomised clinical care comprising 984 atrial fibrillation patients of mean age 86 a comparison was made between edoxaban 15 mg/day versus placebo. Edoxaban was associated with significantly lower rates of stroke and systemic embolism than placebo, both in frail elderly patients(p=0.02 ) and in non frail elderly(p=0.002), respectively.
References
[1]Mitchell A., Watson M., Welsh TJ., McGrogan A
Safety and effectiveness of anticoagulation therapy in older people with atrial fibrillation during exposed and unexposed treatment periods
Heart 2025 doi:10.1136/heartjnl-2024-324763
[2]Eikelboom J,., Merli G
Bleeding with direct oral anticoagulants vs warfarin: clinical experience Am J Med 2016;129S33-S40
[3]Akashi S., Oguri M., Ikeno E et al
Outcomes and afety of very low dose edoxaban in frail patients with atrial fibrillation in the ELDERCARE-AF randomised clinical trial
JAMA Network Open 2o22;5;e2228500
Due to the considerable degree of overlap between stigmata of cardiac sarcoidosis(CS) and idiopathic giant cell myocarditis(IGCM)[1], an evaluation of the association of CS and arrhythmogenic cardiomyopathy(ACM)[2] should be accompanied by a caveat acknowledging the potential for an association along the same lines also to exist between ACM and IGCM. The evidence which supports such an association is to be found in the study which showed a reduction in immunoreactive signal for the desmosomal protein plakoglobin at the cardiac myocyte junctions not only in patients with CS but, also, in patients with IGCM[3].
The following are some of the parallels between CS, IGCM, and ACM:-
(i)The atrioventricular(AV) conduction derangements which characterise the association of CS and ACM[2] have , as their counterpart, the AV conduction defects documented in CS and in IGCM, respectively[4], and also in ACM, on its own.{5].
(ii)Interventricular septum involvement documented in some of the patients with the association of CS and ACM[2] has, as its counterpart, interventricular septal infiltration by IGCM[6], and by ACM[7].
(iii)Finally, extensive myocardial fibrosis, sometimes associated with concomitant replacement of myocardium by adipocytes, may be a feature of CS[8]. It may also be a feature of IGCM(without concomitant adipocyte infiltration)[9], and may be a feature of ACM even in the absence of concomitant adipocyte infiltration[10].
For all t...
Due to the considerable degree of overlap between stigmata of cardiac sarcoidosis(CS) and idiopathic giant cell myocarditis(IGCM)[1], an evaluation of the association of CS and arrhythmogenic cardiomyopathy(ACM)[2] should be accompanied by a caveat acknowledging the potential for an association along the same lines also to exist between ACM and IGCM. The evidence which supports such an association is to be found in the study which showed a reduction in immunoreactive signal for the desmosomal protein plakoglobin at the cardiac myocyte junctions not only in patients with CS but, also, in patients with IGCM[3].
The following are some of the parallels between CS, IGCM, and ACM:-
(i)The atrioventricular(AV) conduction derangements which characterise the association of CS and ACM[2] have , as their counterpart, the AV conduction defects documented in CS and in IGCM, respectively[4], and also in ACM, on its own.{5].
(ii)Interventricular septum involvement documented in some of the patients with the association of CS and ACM[2] has, as its counterpart, interventricular septal infiltration by IGCM[6], and by ACM[7].
(iii)Finally, extensive myocardial fibrosis, sometimes associated with concomitant replacement of myocardium by adipocytes, may be a feature of CS[8]. It may also be a feature of IGCM(without concomitant adipocyte infiltration)[9], and may be a feature of ACM even in the absence of concomitant adipocyte infiltration[10].
For all those reasons a worthwhile follow up of the study by Asimaki et al would be an exploration of the relationship between ACM and IGCM along the same lines and using the same methodology as the exploration of the relationship between CS and ACM[2].
References
[1]Birnie DH., Nair V., Veinot JP
Cardiac sarcoidosis and giant cell myocarditis: Actually, 2 ends of the same disease?
J Am Heart Assoc 2021;10:e020542
[2]Rossi AV., Palazzini M., Ammirati E rt al
Coexistence of cardiac sarcoidosis and arrhythmogenic cardiomyopathy-associated genetic variants: a multicentre case-control study
Heart 2025 doi:10.1136/heartjnl-2024-324525
[3]Asimaki A., Tandri H., Duffy ER et al
Altered desmosomal proteins in granulomatous myocarditis and potential pathogenic links to arryhthmogenic right ventricular cardiomyopathy
Circ Arrhythm Electrophysiol 2011;4:743-752
[4]Kandolin R., Lehtonen J., Kupari M
Cardiac sarcoidosis and giant cell myocarditis as causes of atrioventricular block in young and middle aged adults
Circ Arrhythm Electrophysiol 2011;4:303-309
[5]Liang E., Wu L., Fan S et al
Bradyarrhythmias in arrhythmogenic right ventricular cardiomyopathy
Am J Cardiol 2019;123:1690-1695
[6]Iturriagagotia A., Meert V., De Cocker J et al
progressive thinning of the basal interventricular septum by giant cell myocarditis
JACC Case Reports 2020;2:180-185
[7]Noorman M., Groeneweg JA., Asimaki A et al
End stage arrhythmogenic cardiomyopathy with severe involvement of the interventricular septum
Heart Rhythm 2013;10:283-289
[8]Petrovic M., Buja LM., Kar B et al
Cardiac sarcoidosis presenting as arrhythmogenic right ventricular cardiomyopathy/dysplasia with ventricular aneurysms: a case report
Cardiovascular Pathology 2018;33:1-5
[9]Yokoyama H., Yamaguchi M., Tobita K., Saito S
Different reverse remodeling between left ventricle and right ventricle in fulminating heart failure due to giant cell myocarditis: acas report
Eur Heart J Case Reports 2021;S(8): 1-7
[10]Navarro-Manchon J., Fernandez E., Igual B et al
Left dominant arrhythmogenic cardiomyopathy caused by a novel nonsense mutation in desmoplakin
Rev esp Cardiol 2011;64:S30-S34
No evaluation of clot-in-transit would be complete without a recognition of
the triangular relationship between atrial fibrillation(AF), right heart
thrombi(RHT), and pulmonary embolism(PE).
On the one hand, AF(by causing stasis of right atrial blood) is a risk factor for
PE[1]. This can be inferred from the documentation of PE in patients who have
AF in the absence of concurrent deep vein thrombosis(DVT)[2]. On the other
hand, PE is a risk factor for subsequent development of AF[1]. Anecdotal
reports reinforce these observations. In one report. A 70 year old patient with
PE presented with recent onset breathlessness in association with
echocardiographic documentation of right atrial thrombus. During the time
course of the same echocardiographic evaluation the thrombus was seen to
migrate from the right atrium to the right pulmonary artery. Further imaging
by computed tomography pulmonary angiography(CTPA) was deemed
unnecessary, presumably because the RHT had reached its final destination.
These observations have the potential to generate fundamental differences in
the approach to the workup of patients with the association of symptoms of PE
and documentation of the presence of clots either in the deep veins or in the
right heart chambers. According to one school of thought the aim of
echocardiography is merely “to support the clinical suspicion of pulmonary
No evaluation of clot-in-transit would be complete without a recognition of
the triangular relationship between atrial fibrillation(AF), right heart
thrombi(RHT), and pulmonary embolism(PE).
On the one hand, AF(by causing stasis of right atrial blood) is a risk factor for
PE[1]. This can be inferred from the documentation of PE in patients who have
AF in the absence of concurrent deep vein thrombosis(DVT)[2]. On the other
hand, PE is a risk factor for subsequent development of AF[1]. Anecdotal
reports reinforce these observations. In one report. A 70 year old patient with
PE presented with recent onset breathlessness in association with
echocardiographic documentation of right atrial thrombus. During the time
course of the same echocardiographic evaluation the thrombus was seen to
migrate from the right atrium to the right pulmonary artery. Further imaging
by computed tomography pulmonary angiography(CTPA) was deemed
unnecessary, presumably because the RHT had reached its final destination.
These observations have the potential to generate fundamental differences in
the approach to the workup of patients with the association of symptoms of PE
and documentation of the presence of clots either in the deep veins or in the
right heart chambers. According to one school of thought the aim of
echocardiography is merely “to support the clinical suspicion of pulmonary
embolism” and that, even in the presence of echocardiographic
documentation of RHT, CTPA is the definitive modality for generating an
unequivocal diagnosis of PE[4]. This point of view does not take recognition of
the observation that nearly 100% of RHT are associated with PE[5], and that,
even in the absence of CTPA, serial imaging by echocardiography shows that
the pulmonary circulation is the final destination of RHT[3].
The irony is that, even notwithstanding the fact that CTPA is superior to
echocardiography for detection of RHT, in some patients with either sinus
rhythm or AF, TTE may detect clots in transit across a patent foramen ovale
which were missed by CTPA[6-9]. This matters a lot because, notwithstanding
the successful use of thrombolysis in patients with RHT, embolectomy is the
treatment of choice in the management of patients with impending
paradoxical embolism. The rationale is that , in impending paradoxical
embolism, thrombolysis-related fragmentation of thrombus in transit may
release showers of emboli into the systemic circulation, with adverse
consequences. These observations[6-9], among others, justify routine
deployment of echocardiography(sometimes including transoesophageal
echocardiography) in the workup of suspected PE.
Differences in opinion regarding the relative roles of echocardiography and
CTPA in the workup of patients with symptoms of PE might well have
influenced the decision to omit echocardiography in the workup of a patient
who presented with sudden onset dyspnoea in the presence of AF. Chest X-ray
showed Westermark’s sign(92% specific for PE) and Palla’s sign. However,
instead of undertaking echocardiography to ascertain presence or absence of
RHT(given the fact that AF is a risk factor for RHT)[1], and also instead of
undertaking ultrasonographic evaluation of the limbs for DVT(given the fact
that DVT may be a risk factor for PE irrespective of presence or absence of AF)
the patient was, instead, further evaluated by CTPA, which showed PE[10].
Hypothetically, if either Doppler ultrasonography of the limbs or
echocardiography had disclosed the presence of a clot in the circulation, the
argument that would have prevailed was that the presenting symptom of
recent onset breathlessness signified that the clot had reached the final
destination(ie the pulmonary circulation) and that further imaging by CTPA
was superfluous. Consideration of those issues is relevant to the exercise of
stewardship over the potentially carcinogenic resource of ionising radiation.
References
[1]Nikdell B., Zili MDA., Lip GYH
Pulmonary embolism and atrial fibrillation: Two sides of the same coin?
A systematic Review
Sem Thromb Hemost 2017;43:849-863
[2]Morella P., Sacco M., Carafa M et al
Permanent atrial fibrillation and pulmonary embolism in elderly patients
without deep vein thrombosis: is there a relationship?
Aging Clinical and Experimental Research 2019;31:1121-1128
[3]Hussain B., Sultan FAT., Shahzad T., Pumjani S
Caught in the act-Migration of a large right atrial thrombus to the pulmonary
artery during transthoracic echocardiography: A case report
J Pak Med Assoc 2017;67:1927-1929
[4]Vogiatzis I., Dapcevic I., Sachpekidis V et al
Successful thrombolysis of right atrial and ventricular thrombi in a patient with
massive pulmonary embolism
HIPPOCRATA 2009;13:178-180
[5]Rose PS., Punjabi NM., Pearse DB
Treatment of right heart thromboemboli
CHEST 2002;121:806-814
[6]Nan J., Tan N., Schaff H et al
A dangerous dilemma
Thrombus in transit during pregnancy
JACC 2019;1:369-371
[7]Mensah A., Ogunbayo G., Patel P
Arrested in the act: Pulmonary embolism with right atrial thrombus-in-transit
across a patent foramen ovale
CHEST 2015;148;980 A doi.101378/chest.2281077
[8]Nombera N., Guearra M., Alvorado M a de los Angeles G., Benal MA
A thrombus trapped in a patent foramen ovale: a migrant out of the
ordinary
Archivos de Cardiologia de Mexico 2023;93:500-501
[9]Ishihara T., Hara H., Saijo T et al
Left atrial thrombus causing pulmonary embolism by passing through an
atrial septal defect
Circulation Journal 2002;66:109-110
[10] Shumoyama T., Tomoda Y
Westermark’s sign and Palla’s sign in pulmonary embolism
New England Journal of Medicine 2025;DOI:10.1056/NEJM icm
2409241
No evaluation of the association between NT-pro BNP levels and risk of atrial fibrillation(AF) can ever be complete without a recognition of the triangular relationship between AF, renal function, and natriuretic peptide levels.
The starting point is a recognition that impairment of renal function is a risk factor for incident AF(and vice versa) and that a fall in glomerular filtration rate is associated with an increase in NT-pro BNP levels.
The formula for estimated glomerular filtration rate(eGFR) which most accurately shows that impairment of eGFR confers higher risk of incident AF is the one that utilises the difference between cystatin C-based eGFR and creatinine-based eGFR[1]. In the latter study, during a median follow up of 11.7 years, it was shown that participants with impaired eGFR had a higher risk of incident AF(subdistirbution Hazard Ratio 1.25; 95% Confidence Interval 1.20 to 1.30)[1]. Using the same formula, other workers showed that prevalent AF was associated with increased risk of incident reduction in renal function(adjusted HR 1.33;95% CI 1.12 to 1.58)[2].
Secondly, there is an association between renal function and natriuretic peptide levels, most likely as a consequence of the fact that 55%-65% of plasma NT pro BNP is cleared by the kidney[3]. Consequently, renal clearance of NT pro BNP is markedly decreased in chronic kidney disease(CKD)[4]. For example, among patients on chronic haemodialysis, eGFR has been shown to be i...
No evaluation of the association between NT-pro BNP levels and risk of atrial fibrillation(AF) can ever be complete without a recognition of the triangular relationship between AF, renal function, and natriuretic peptide levels.
The starting point is a recognition that impairment of renal function is a risk factor for incident AF(and vice versa) and that a fall in glomerular filtration rate is associated with an increase in NT-pro BNP levels.
The formula for estimated glomerular filtration rate(eGFR) which most accurately shows that impairment of eGFR confers higher risk of incident AF is the one that utilises the difference between cystatin C-based eGFR and creatinine-based eGFR[1]. In the latter study, during a median follow up of 11.7 years, it was shown that participants with impaired eGFR had a higher risk of incident AF(subdistirbution Hazard Ratio 1.25; 95% Confidence Interval 1.20 to 1.30)[1]. Using the same formula, other workers showed that prevalent AF was associated with increased risk of incident reduction in renal function(adjusted HR 1.33;95% CI 1.12 to 1.58)[2].
Secondly, there is an association between renal function and natriuretic peptide levels, most likely as a consequence of the fact that 55%-65% of plasma NT pro BNP is cleared by the kidney[3]. Consequently, renal clearance of NT pro BNP is markedly decreased in chronic kidney disease(CKD)[4]. For example, among patients on chronic haemodialysis, eGFR has been shown to be inversely correlated with NT-pro BNP levels(r=-0.579; p <0.0001)[5]. In another study, among subjects with systolic heart failure, NT-pro BNP levels were four times higher in CKD stage 5 patients compared with patient in stage 3 CKD[6].
Previous proposals for the use of cardiovascular biomarkers as an adjunct to the CHA2 DS2 Vasc score involved the use of troponin I as well as NT pro BNP[7]. The caveat regarding the use of troponin is that troponin levels, too, are affected by renal function[8]. In the latter study, among patients with CKD who did not have acute coronary syndrome, as many as 38% subjects had cardiac troponin I levels above 99th percentile of healthy controls, and 68% had cardiac troponin T levels above the 99th percentile of healthy controls[8].
Accordingly, the use of either NT pro BNP or cardiac troponin I for stratification of the risk of incident AF should take account of the confounding effect of renal dysfunction. The latter, in turn , is influenced by parameters such as age and hypertension[9], both of which might well be the ultimate determinants of AF-related renal dysfunction.
I have no conflict of interest.
References
[1]Heo GY., Koh HB., Jung C-Y et al
Difference between estimated GFR based on cystatin C versus Creatinine and incident atrial fibrillation: A cohort study of the UK biobank
AJKD 2024;83:729-738
[2] van der Burgh AC., Geurts S., Ikram MA et al
Bidirectional association between kidney function and atrial fibrillation: a population-based cohort study
Journal of the American Heart Association 2022;11;e025303
[3]Palmer SC., Yandle TG., Nicholls G., Frampton CM., Richards AM
Regional clearance of amino terminal pro-brain natriuretic peptide from human plasma
European Journal of Heart Failure 2009;11:832-839
[4]Tsutamoto T., Sakai H., Yamamoto T., Nakagawa Y
Renal clearance of N-terminal pro-B Brain Natriuretic Peptide is markedly decreased in chronic kidney disease
Circ Rep 2019;1:326-332
[5]Takase H., Dohi Y
Kidney function crucially affects B-type natriuretic peptide(BNP), N-terminal pro BNP and their relationship
European Journal of Clinical Investigation 2014;44:303-308
[6]Jafri L., Kashif W., Tai J et al
B-type natriuretic peptide versus amino terminal pro-B type natriuretic peptide: selcting the optimal heart failure marker in patints with impaired kidney function
BMC Nephrology 2013;14:117
[7]Ruff CT., Giugliano RP., Braunwald E et al
Cardiovascular biomarker score and clinical outcomes in patients with atrial fibrillation
A subanalysis of the ENGAGE AF-TIMI 48 randomized clinical trial
JAMA Cardiology 2016;1:999-1006
[8]de Filippi C., Seliger SL., Kelley W et al
Interpreting cardiac troponin results from high-sensitivity assays in chronic kidney disease without acute coronary syndrome
Clinical; Chemistry 2012;58:1342-1351
[9]Lindeman RD., Tobin JD., Shock NW
Association between blood pressure and rate of decline in renal function with age
Kidney International 1984;26:861-868
Intriguingly, in the recent study, severe mitral regurgitation was present in as many as 10.3% of patients who did not have left ventricular outflow tract obstruction(LVOTO)[1]. This observation raises the question of whether or not mitral regurgitation(MR) might, in some of those cases, have been attributable to Takotsubo-related tethering of the mitral valve leaflets[2]. The latter was the underlying cause of severe MR in a 57 year old woman with previous history of treated hypertension who presented with chest pain and a blood pressure of 119/84 mm Hg. What we do not know is whether or not that blood pressure was her usual "on treatment" blood pressure or whether it represented a significant fall from her usual blood pressure. Her electocardiogram(ECG) showed ST segment elevation in leads V5 and V6. Coronary angiography did not show any obstructive lesion. Instead, she had stigmata of TTC, namely, apical left ventricular apical hypokinesis and basal hyperkinesis. Furthermore, she had eccentric mitral regurgitation associated with tethering of the anterior mitral leaflet. Neither LVOTO nor systolic anterior motion(SAM) of the mitral valve was observed. Her left ventricular ejection fraction(LVEF) amounted to 59.7%. After an uneventful clinical course she had a follow up which showed complete resolution of MR[2]. Leaflet tethering is believed also to be implicated in the aetiopathogenesis of TTC-related tricuspid regurgitation(TR)[3]. On occasions...
Intriguingly, in the recent study, severe mitral regurgitation was present in as many as 10.3% of patients who did not have left ventricular outflow tract obstruction(LVOTO)[1]. This observation raises the question of whether or not mitral regurgitation(MR) might, in some of those cases, have been attributable to Takotsubo-related tethering of the mitral valve leaflets[2]. The latter was the underlying cause of severe MR in a 57 year old woman with previous history of treated hypertension who presented with chest pain and a blood pressure of 119/84 mm Hg. What we do not know is whether or not that blood pressure was her usual "on treatment" blood pressure or whether it represented a significant fall from her usual blood pressure. Her electocardiogram(ECG) showed ST segment elevation in leads V5 and V6. Coronary angiography did not show any obstructive lesion. Instead, she had stigmata of TTC, namely, apical left ventricular apical hypokinesis and basal hyperkinesis. Furthermore, she had eccentric mitral regurgitation associated with tethering of the anterior mitral leaflet. Neither LVOTO nor systolic anterior motion(SAM) of the mitral valve was observed. Her left ventricular ejection fraction(LVEF) amounted to 59.7%. After an uneventful clinical course she had a follow up which showed complete resolution of MR[2]. Leaflet tethering is believed also to be implicated in the aetiopathogenesis of TTC-related tricuspid regurgitation(TR)[3]. On occasions moderately severe TTC-related TR may coexist with moderately severe TTC-related MR[4].
Severe MR can also be a manifestation of the coexistence of TTC and hitherto unrecognised hypertrophic obstructive cardiomyopathy(HOCUM)[5] In the latter example the patient presented with hypotension, and the echocardiogram showed apical hypokinesia and "massive" MR associated with SAM of the mitral valve. Dynamic left ventricular outflow tract gradient amounted to 250 mm Hg. Endomyocardial biopsy showed hypertrophied and bizarre myocytes with myocyte disarray, in addition to histological changes often documented in TTC[5]
In the presence of cardiogenic shock the differential diagnosis of MR also includes TTC-related papillary muscle rupture(PMR)[6],[7],[8]. Paradoxically, in one case, despite the presence of hypotension(blood pressure 90/50 mm Hg) and heart rate of 160/minute, echocardiography only showed mild to moderate MR. Nevertheless PMR was documented, in addition to apical hypokinesia and basal hyperkinesis. LVEF amounted to 20%, and no stenosis was documented on coronary angiography. The patient was managed with dobutamine and diuretics, followed by surgical repair of the mitral valve apparatus. Initial management with vasoppressors was also deployed in a 36 year old woman with PMR giving rise to flail posterior mitral leaflet[7]. In Yaghoubi et al a 36 year old woman presented without any ST segment changes, even after recovery from a cardiac arrest. Echocardiography showed severe MR and mid to distal left ventricular hypokinesia. Coronary angiography did not show any abnormality.. Surgical intervention disclosed rupture of the chordae tendinae group of the anterior papillary muscle[8].
References
I have no conflict of interest.
References
[1]Villa-Sanjuan S., Nunez-Gil IJ., Vedia O et al
Left ventricular outflow tract obstruction in Takotsubo syndrome with cardiogenic shock prognosis and treatment
Heart 2024;Epub ahead of print
[2]Nonala D., Takase H., Machii M., Ohno K
Intraventricular thrombus and severe mitral regurgitation in the acute phase of takotsubo cardiomyopathy: two case reports
Journal of Medical Case Reports 2029;13: 152
[3]Sumida H., Morihisa K., Katahira K et al
Isolated right ventricular stress(Takotsubo) cardiomyopathy
Internal Medicine 2017;56:2159-2164
[4]Lee WLS., Li-fu M., Chan HWR., Chen M-z
Takotsubo syndrome with transient complete atrioventricular block
Chinese Medical Journal 2006;
[5]Arakawa K., Gondo T., Matsushita K et al
Takotsubo cardiomyopathy in a patient with previously undiagnosed hyperterophic cardiomyopathy with latent obstruction
Intern Med 2018;57:2969-2973
[6]Nef HM., Mollmann H., Hilpert P et al
Severe mitral regurgitation in Tako-Tsubo cardiomyopathy
Int J Cardiol 2009;132:e77-e78
[7]Chen D., Abi-Hanna D., Lambros J
Rupture of s broken heart: A rare cause of acute mitral regurgitation due to papillary muscle rupture complicating Takotsubo cardiomyopathy
Eur Heart J Cardiovascular Imaging 2020;21:suppl(1 P 1297)
[8]Yaghouibi AR., Ansarin K., Hashemxadeh S et al
Takotsubo cardiomyopathy induced by emotional stress leading to severe mitral regurgitation
Int J Cardiol 2009;135:e85-e86
The health and wellbeing of an individual are shaped by many factors. Although this valuable study (1) focusses on elevated risk of sudden cardiac death (SCD) in patients with psychiatric disorders, and adjusts for age, sex and comorbidities, multiple other variables and risk factors were not considered; these may be outside of the remit of this study.
Multiple variables and multiple other risk factors may interact, and interplay, all of which could affect the outcome of SCD in patients with psychiatric disorders. These include genetic factors, family history of cardiovascular disease and a personal history of cardiovascular diseases. Multiple cardiometabolic risk factors (risk factors include hypertension, diabetes, elevated cholesterol/ lipid levels and smoking) predisposes individuals to SCD.
The health of respiratory system and other vital organs (liver, kidneys, gut health) can modulate or indirectly affect cardiometabolic disease, which can lead to SCD. For example, COPD have a 34% increased risk of SCD overall, but the risk almost doubles more than five years after first being diagnosed with COPD. The risk of SCD increases more than three-fold after five years, in COPD patients who have frequent exacerbations (2).
Although the above-named risk factors shape the outcome of cardiovascular diseases and SCD, the most important variables are related to the social determinants of health (SDH). The health and wellbeing of an individual are shaped by SDH....
The health and wellbeing of an individual are shaped by many factors. Although this valuable study (1) focusses on elevated risk of sudden cardiac death (SCD) in patients with psychiatric disorders, and adjusts for age, sex and comorbidities, multiple other variables and risk factors were not considered; these may be outside of the remit of this study.
Multiple variables and multiple other risk factors may interact, and interplay, all of which could affect the outcome of SCD in patients with psychiatric disorders. These include genetic factors, family history of cardiovascular disease and a personal history of cardiovascular diseases. Multiple cardiometabolic risk factors (risk factors include hypertension, diabetes, elevated cholesterol/ lipid levels and smoking) predisposes individuals to SCD.
The health of respiratory system and other vital organs (liver, kidneys, gut health) can modulate or indirectly affect cardiometabolic disease, which can lead to SCD. For example, COPD have a 34% increased risk of SCD overall, but the risk almost doubles more than five years after first being diagnosed with COPD. The risk of SCD increases more than three-fold after five years, in COPD patients who have frequent exacerbations (2).
Although the above-named risk factors shape the outcome of cardiovascular diseases and SCD, the most important variables are related to the social determinants of health (SDH). The health and wellbeing of an individual are shaped by SDH. These include the social, environment, and physical environments in which these individuals live.
Research has established that inequalities in SDH factors such as housing, education, wealth, employment and social support can all influence health outcomes in psychiatric disorders including both common mental disorders (CMD) like depression, and severe mental illness (SMI) like schizophrenia, leading to higher risk of poorer health and premature deaths.
The lack of equitable distribution of health affects marginalised people with psychiatric disorders. Addressing differences in SDH can help accelerate progress towards health equity (Equity is a state in which every individual could attain optimum level of health and wellbeing).
SDH have been shown to have greater influence on health, more important than access to healthcare service, lifestyle factors or genetic factors. For example, numerous studies suggest that SDH account for between 30-55% of health outcomes. In addition, estimates show that the contribution of sectors outside health to population health outcomes exceeds the contribution from the health sector (3).
Moreover, SDH combined with SMI leads to social drift (refer to the social drift hypothesis) which again indirectly leads to poorer health in these individuals. Social drift leads to poverty. And poverty is highly correlated with poor health and premature death, more so in certain ethnic groups.
CDC’s (Centre for Disease Control) Racial and Ethnic Approaches to Community Health (REACH) focuses on reducing elevated rates of chronic diseases for specific racial and ethnic groups in various communities. It aims to improve health, prevent chronic diseases, and reduce health disparities among racial and ethnic populations with the highest risk, or burden, of chronic disease. Such diseases include high blood pressure, heart disease, type 2 diabetes, and obesity (4).
Addressing the variables related to SDH via government policies such as poverty alleviation programmes, improving education, providing adequate housing, coordinating access to healthcare, can go a long way in reducing cardiometabolic adverse outcomes in schizophrenia and other severe mental health disorders (5).
References:
1. Mujkanovic J, Warming PE, Kessing LV, et al. Nationwide burden of sudden cardiac death among patients with a psychiatric disorder. Heart. Published Online First: 22 October 2024. doi: 10.1136/heartjnl-2024-324092
2. Lahousse L, et al. Chronic obstructive pulmonary disease and sudden cardiac death; the Rotterdam study. European Heart Journal. Doi:10.1093/eurheartj/ehv121.
3. https://www.who.int/health-topics/social-determinants-of-health#tab=tab_1.
4. CDC’s (Centre for Disease Control) Racial and Ethnic Approaches to Community Health (REACH): https://www.cdc.gov/reach/php/reach-2023-2028/index.html.
5. Lund C, De Silva M, Plagerson S, Cooper S, Chisholm D, Das J, Knapp M, Patel V. Poverty and mental disorders: breaking the cycle in low-income and middle-income countries. Lancet 2011; 378:1502-14.
The point is well made(even in passing) that iron deficient heart failure patients assigned to treatment with intravenous iron experience significantly lower rates of infection than counterparts not allocated to that treatment modality[1]. Even outside the context of congestive heart failure(CHF) iron deficiency has been shown to be associated with increased risk of infection[2]. The latter study explored the risk of infection according to levels of serum iron, transferrin saturation(TS), and serum ferritin. After multivariate adjustment, low TS at or below the fifth percentile(ie TS 11% or below) was associated with increased risk of any infection compared with TS between the 26th and the 74th percentile(ie TS 18.1-27.9)(Hazard Ratio 1.18; 95% Confidence Interval 1.10-1.26). More specifically, in that study , where >90% of infection-related deaths were attributable to pneumonia, low TS was also associated with increased risk of pneumonia(Hazard Ratio 1.20;95% CI 1.09-1.32)[2]..
In the cardiology context, infective endocarditis(IE), a disorder often complicated by CHF, can, itself, occur in association with iron deficiency(ID).
The following are examples of the association of IE and ID:-
(i)Association of IE and nutritional ID was documented in a 19 year old woman with a history of volitional anorexia and wight loss.
Iron deficiency was characterised by TS of 10%. She was initially given a diagnosis of anorexia nervosa and was pr...
Show MoreBridging the Gap: Improving Iron Deficiency Management in Heart Failure
The article by Su et al. offers an in-depth exploration of the persistent gaps in the knowledge and management of iron deficiency (ID) among cardiologists treating heart failure (HF) patients in China. This study not only highlights deficiencies in adherence to evidence-based guidelines but also underscores systemic and educational barriers that hinder optimal care.
The findings are striking: over half of the cardiologists surveyed were unaware of the need to routinely screen for ID in HF patients, and only a fraction understood the critical diagnostic role of transferrin saturation (TSAT). Alarmingly, less than 1% identified TSAT <20% as a standalone criterion for diagnosing ID, despite its established prognostic significance. This lack of awareness reflects a larger, global challenge in implementing ID management protocols, which are consistently linked to improved outcomes in HF patients.
Equally concerning is the predominant reliance on oral iron supplementation, with 68% of respondents favoring it over intravenous (IV) iron. This preference persists despite robust evidence from clinical trials demonstrating the superior efficacy of IV iron in improving functional capacity, quality of life, and reducing HF hospitalizations. Barriers to IV iron use—ranging from limited availability of recommended formulations like ferric carboxymaltose to misconceptions about adverse effects—f...
Show MoreTo the editor: Zhang et al. provide a fascinating observational study showing that weight loss among obese UK Biobank participants with cardiovascular disease may not be beneficial [1]. The authors specifically highlight the following point “Maintaining a stable weight in obese people with cardiovascular disease may reduce the risk of mortality” [1]. Evidence from a large trial has shown that the weight loss drug semaglutide reduces mortality amongst the overweight/obese with pre-existing cardiovascular disease [2]. It is possible that some of the benefits of semaglutide could be driven by factors other than weight loss, given some benefits are evident before substantial weight has occurred [2]. However, some of the benefits of semaglutide are undoubtedly due to weight loss making Zhang et al.’s observations puzzling.
Zhang at al.’s study is an observational study of weight change in obese people with cardiovascular disease [1], so it is essentially a case series. Inference from case series is seen as the least reliable type of observational evidence [3]. Correspondingly, Zhang et al.’s study of the role of weight change in obese people with cardiovascular disease [1] is open to both the major sources of bias in causal inference, i.e., to confounding and selection bias [4].
Specifically, Zhang et al.’s study is open to confounding by obesity because obesity is likely a common cause of weight change and death. The study is also open to selection bias because...
Show MoreEconomou Lundeberg et al report a U-shaped association between individuals estimated sodium intake and premature ventricular complexes (1). The estimate of individual sodium intake is based on a single fasting spot urine sodium value and the Kawasaki formula (1). The authors claim that the method is valid in part because the urine samples were collected in the fasting state and that the results have a correlation with 24-hr urine sodium excretion and blood pressure (1).
However, extensive consistent evidence, as repeatedly reviewed by major international scientific organizations, indicates single spot urine sodium values with estimating equations (including those using fasting urine samples and the Kawasaki equation) are not a valid method of assessing an individual’s dietary sodium (2-4). The method has very high random and systematic errors (2, 4, 5). The systematic errors have been shown to alter a linear association of dietary sodium and health outcomes (blood pressure and cardiovascular disease) including to a U or J shaped curve and to have associations with health outcomes when a constant sodium value is inserted in the equation rather than a real value (2-5). The changes in disease associations and disease associations independent of the sodium variable have been shown in several data bases and are mathematically predictable.
The random error is reflected by very low accuracy and reproducibility. For example, in a reanalysis of the validation of...
Show MoreGiven the disparity between the number of patients in apixaban(4261 patients) and the number of patients on edoxaban(76 patients)[1] it was not possible to make a meaningful comparison between the two agents especially because, in other contexts, edoxaban has been utilised in doses ranging from 15 mg/day to 6o mg/day in people with atrial fibrillation(AF){2],{3]. Accordingly, to lump edoxaban with other direct oral anticoagulants(DOACS) in the comparison with warfarin, as Mitchell et al have done(fig 4)[1[] does not do justice to the safety profile of edoxaban.
Show MoreIn the comparison undertaken by Eikelboom et al between the safety profile of warfarin and individual DOACs the 30 mg/day dose of edoxaban was cited as being associated with significantly lower risk of gastrointestinal bleeding than warfarin(Hazard Ratio 0.67; 95% Confidence Interval 0.53-0.83)[2]. This was the dose recommended in patients with body weight 60 kg or less[2].
In the ELDERCARE-AF randomised clinical care comprising 984 atrial fibrillation patients of mean age 86 a comparison was made between edoxaban 15 mg/day versus placebo. Edoxaban was associated with significantly lower rates of stroke and systemic embolism than placebo, both in frail elderly patients(p=0.02 ) and in non frail elderly(p=0.002), respectively.
References
[1]Mitchell A., Watson M., Welsh TJ., McGrogan A
Safety and effectiveness of anticoagulation therapy in older people with atrial fibrillation d...
Due to the considerable degree of overlap between stigmata of cardiac sarcoidosis(CS) and idiopathic giant cell myocarditis(IGCM)[1], an evaluation of the association of CS and arrhythmogenic cardiomyopathy(ACM)[2] should be accompanied by a caveat acknowledging the potential for an association along the same lines also to exist between ACM and IGCM. The evidence which supports such an association is to be found in the study which showed a reduction in immunoreactive signal for the desmosomal protein plakoglobin at the cardiac myocyte junctions not only in patients with CS but, also, in patients with IGCM[3].
Show MoreThe following are some of the parallels between CS, IGCM, and ACM:-
(i)The atrioventricular(AV) conduction derangements which characterise the association of CS and ACM[2] have , as their counterpart, the AV conduction defects documented in CS and in IGCM, respectively[4], and also in ACM, on its own.{5].
(ii)Interventricular septum involvement documented in some of the patients with the association of CS and ACM[2] has, as its counterpart, interventricular septal infiltration by IGCM[6], and by ACM[7].
(iii)Finally, extensive myocardial fibrosis, sometimes associated with concomitant replacement of myocardium by adipocytes, may be a feature of CS[8]. It may also be a feature of IGCM(without concomitant adipocyte infiltration)[9], and may be a feature of ACM even in the absence of concomitant adipocyte infiltration[10].
For all t...
No evaluation of clot-in-transit would be complete without a recognition of
the triangular relationship between atrial fibrillation(AF), right heart
thrombi(RHT), and pulmonary embolism(PE).
On the one hand, AF(by causing stasis of right atrial blood) is a risk factor for
PE[1]. This can be inferred from the documentation of PE in patients who have
AF in the absence of concurrent deep vein thrombosis(DVT)[2]. On the other
hand, PE is a risk factor for subsequent development of AF[1]. Anecdotal
reports reinforce these observations. In one report. A 70 year old patient with
PE presented with recent onset breathlessness in association with
echocardiographic documentation of right atrial thrombus. During the time
course of the same echocardiographic evaluation the thrombus was seen to
migrate from the right atrium to the right pulmonary artery. Further imaging
by computed tomography pulmonary angiography(CTPA) was deemed
unnecessary, presumably because the RHT had reached its final destination.
These observations have the potential to generate fundamental differences in
...Show Morethe approach to the workup of patients with the association of symptoms of PE
and documentation of the presence of clots either in the deep veins or in the
right heart chambers. According to one school of thought the aim of
echocardiography is merely “to support the clinical suspicion of pulmonary
No evaluation of the association between NT-pro BNP levels and risk of atrial fibrillation(AF) can ever be complete without a recognition of the triangular relationship between AF, renal function, and natriuretic peptide levels.
Show MoreThe starting point is a recognition that impairment of renal function is a risk factor for incident AF(and vice versa) and that a fall in glomerular filtration rate is associated with an increase in NT-pro BNP levels.
The formula for estimated glomerular filtration rate(eGFR) which most accurately shows that impairment of eGFR confers higher risk of incident AF is the one that utilises the difference between cystatin C-based eGFR and creatinine-based eGFR[1]. In the latter study, during a median follow up of 11.7 years, it was shown that participants with impaired eGFR had a higher risk of incident AF(subdistirbution Hazard Ratio 1.25; 95% Confidence Interval 1.20 to 1.30)[1]. Using the same formula, other workers showed that prevalent AF was associated with increased risk of incident reduction in renal function(adjusted HR 1.33;95% CI 1.12 to 1.58)[2].
Secondly, there is an association between renal function and natriuretic peptide levels, most likely as a consequence of the fact that 55%-65% of plasma NT pro BNP is cleared by the kidney[3]. Consequently, renal clearance of NT pro BNP is markedly decreased in chronic kidney disease(CKD)[4]. For example, among patients on chronic haemodialysis, eGFR has been shown to be i...
Intriguingly, in the recent study, severe mitral regurgitation was present in as many as 10.3% of patients who did not have left ventricular outflow tract obstruction(LVOTO)[1]. This observation raises the question of whether or not mitral regurgitation(MR) might, in some of those cases, have been attributable to Takotsubo-related tethering of the mitral valve leaflets[2]. The latter was the underlying cause of severe MR in a 57 year old woman with previous history of treated hypertension who presented with chest pain and a blood pressure of 119/84 mm Hg. What we do not know is whether or not that blood pressure was her usual "on treatment" blood pressure or whether it represented a significant fall from her usual blood pressure. Her electocardiogram(ECG) showed ST segment elevation in leads V5 and V6. Coronary angiography did not show any obstructive lesion. Instead, she had stigmata of TTC, namely, apical left ventricular apical hypokinesis and basal hyperkinesis. Furthermore, she had eccentric mitral regurgitation associated with tethering of the anterior mitral leaflet. Neither LVOTO nor systolic anterior motion(SAM) of the mitral valve was observed. Her left ventricular ejection fraction(LVEF) amounted to 59.7%. After an uneventful clinical course she had a follow up which showed complete resolution of MR[2]. Leaflet tethering is believed also to be implicated in the aetiopathogenesis of TTC-related tricuspid regurgitation(TR)[3]. On occasions...
Show MoreThe health and wellbeing of an individual are shaped by many factors. Although this valuable study (1) focusses on elevated risk of sudden cardiac death (SCD) in patients with psychiatric disorders, and adjusts for age, sex and comorbidities, multiple other variables and risk factors were not considered; these may be outside of the remit of this study.
Show MoreMultiple variables and multiple other risk factors may interact, and interplay, all of which could affect the outcome of SCD in patients with psychiatric disorders. These include genetic factors, family history of cardiovascular disease and a personal history of cardiovascular diseases. Multiple cardiometabolic risk factors (risk factors include hypertension, diabetes, elevated cholesterol/ lipid levels and smoking) predisposes individuals to SCD.
The health of respiratory system and other vital organs (liver, kidneys, gut health) can modulate or indirectly affect cardiometabolic disease, which can lead to SCD. For example, COPD have a 34% increased risk of SCD overall, but the risk almost doubles more than five years after first being diagnosed with COPD. The risk of SCD increases more than three-fold after five years, in COPD patients who have frequent exacerbations (2).
Although the above-named risk factors shape the outcome of cardiovascular diseases and SCD, the most important variables are related to the social determinants of health (SDH). The health and wellbeing of an individual are shaped by SDH....
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